Improvements in cancer screening effectiveness, higher participation rates and faster introduction of new screening tests could have pronounced effects on the health of the community by reducing cancer burden. Cancer screening effectiveness in real-world settings depends not only on the efficacy of individual tests but also on patients, health care providers, and the systems and context in which health care is delivered. Large and well defined populations of enrollees with diverse data sources are fundamental for comparative effectiveness research that addresses health policy questions about cancer screening delivery. In response to the Grand Opportunity (GO), we propose to create an innovative and sustainable multi-disciplinary and multi-institutional virtual center for cancer SEARCH: Screening Effectiveness And Research in Community-based Healthcare within the NCI-funded Cancer Research Network (CRN). Because SEARCH is set in CRN-affiliated health care delivery systems across the United States, it will benefit directly from the strong foundation of an existing and well-established network of NCI-funded research infrastructure. An innovative portion of SEARCH will be our ability to translate and disseminate of our findings directly into practice. We have identified and engaged a national Advisory Board of cancer screening experts and have proposed a new collaboration with the Cancer Intervention and Surveillance Modeling Network (CISNET). Together, we will pursue high priority comparative effectiveness research (CER) that has relevance to clinicians, patients, policy makers, payers, public health practitioners and medical associations. Our specific aims over the two-year grant period are to: 1) Create a multi-disciplinary, multi-site team for CER focused on the delivery of cancer screening in community-based settings;2) Develop methodological capacity for future large-scale, population-based CER studies;3) Demonstrate our ability to conduct CER in the area of cancer screening to address important evidence gaps. Eight CRN sites will be involved in this application with four sites (Group Health, Kaiser Northwest and Hawaii, and Fallon) contributing data for the proof of principle studies. We expect SEARCH will serve as a productive platform for launching larger CER studies. During the two year funding period, we will build necessary infrastructure and collaborations, and will seek additional funding to address important questions on the quality and effectiveness of cancer screening care delivery in community-based health care systems. PUBLIC HEALTH RELEVANCE: Large and well defined populations of enrollees with diverse data sources are fundamental for comparative effectiveness research that addresses health policy questions about cancer screening delivery. We plan to study approaches to effectively deliver cancer screening to populations in order to enhance detection, diminish morbidity and other adverse effects, and ultimately reduce mortality. The SEARCH: Screening Effectiveness And Research in Community-based Healthcare research team will be based within the geographically diverse health care systems of the NCI-funded Cancer Research Network, which is a consortium of 14 health plans across the US, and will enable translation of our findings directly into clinical practice in community settings.